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Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity

Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity


Title: Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
Author: Myszor, Iwona T.
Parveen, Zahida
Ottosson, Håkan
Bergman, Peter
Agerberth, Birgitta
Strömberg, Roger
Guðmundsson, Guðmundur H.
Date: 2019-05-08
Language: English
Scope: 7114
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: Scientific Reports;9(1)
ISSN: 2045-2322
DOI: 10.1038/s41598-019-43350-z
Subject: Cell signalling; Innate immunity; Ónæmisfræði; Frumulíffræði
URI: https://hdl.handle.net/20.500.11815/1571

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Citation:

Myszor, I.T., Parveen, Z., Ottosson, H. et al. Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity. Scientific Reports 9, 7114 (2019). https://doi.org/10.1038/s41598-019-43350-z

Abstract:

Aroylated phenylenediamines (APDs) are novel inducers of innate immunity enhancing cathelicidin gene expression in human bronchial epithelial cell lines. Here we present two newly developed APDs and aimed at defning the response and signaling pathways for these compounds with reference to innate immunity and antimicrobial peptide (AMP) expression. Induction was initially defned with respect to dose and time and compared with the APD Entinostat (MS-275). The induction applies to several innate immunity efectors, indicating that APDs trigger a broad spectrum of antimicrobial responses. The bactericidal efect was shown in an infection model against Pseudomonas aeruginosa by estimating bacteria entering cells. Treatment with a selected APD counteracted Pseudomonas mediated disruption of epithelial integrity. This double action by inducing AMPs and enhancing epithelial integrity for one APD compound is unique and taken as a positive indication for host directed therapy (HDT). The APD efects are mediated through Signal transducer and activator of transcription 3 (STAT3) activation. Utilization of induced innate immunity to fght infections can reduce antibiotic usage, might be efective against multidrug resistant bacteria and is in line with improved stewardship in healthcare.

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Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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